Statins In Intracerbral Hemorrhage (SATURN)

STATINS USE IN INTRACEREBRAL HEMORRHAGE PATIENTS

The SATURN trial aims to determine whether continuation vs. discontinuation of statin drugs after spontaneous lobar intracerebral hemorrhage (ICH) is the best strategy; and whether the decision to continue/discontinue statins should be influenced by an individual's Apolipoprotein-E (APOE) genotype.

An MRI ancillary study (SATURN MRI), in a subset of SATURN participants , will evaluate the effects of continuation vs. discontinuation of statin drugs on hemorrhagic and ischemic MRI markers of cerebral small vessel disease, and whether the presence/burden of hemorrhagic markers (i.e. cerebral microbleeds and/or cortical superficial siderosis) on baseline MRI influences the risk of ICH recurrence on/off statin therapy.

Study Overview

• Status: Recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Statins

Detailed Description

SATURN is a multi-center, pragmatic, prospective, randomized, open-label, and blinded end-point assessment (PROBE) clinical trial. A total of 1,456 patients presenting within 7 days of a spontaneous lobar ICH while taking statins will be randomized to one of two treatment strategies: discontinuation vs. continuation of statin therapy (using the same agent and dose that they were using at ICH onset). Participating subjects will undergo baseline testing for APOE genotype and will be followed for 24 months to assess for the occurrence of recurrent symptomatic ICH or major adverse cerebro-/cardio-vascular events (MACCE) during the follow-up period. A subset of SATURN participants will participate in the optional MRI study, where they will undergo a baseline MRI within 7 days of randomization into SATURN and a repeat MRI at the end of the follow-up period.

Recruitment will take place at ~ 140 sites coordinated through the NIH/NINDS StrokeNet and the Canadian Stroke Consortium.

• Study Type: Interventional
• Enrollment (Estimated): 1456
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Magdy Selim, MD, PhD; Phone Number: 617-632-8913; Email: mselim@bidmc.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Magdy Selim, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 50 years.
2. Spontaneous lobar ICH confirmed by CT or MRI scan
3. Patient was taking a statin drug at the onset of the qualifying/index ICH
4. Randomization can be carried out within 7 days of the onset of the qualifying ICH
5. Patient or legally authorized representative, after consultation with the statin prescriber, agrees to be randomized to statin continuation (restart) vs. discontinuation

Exclusion Criteria:

1. Suspected secondary cause for the qualifying ICH, such as an underlying vascular abnormality or tumor, trauma, venous infarction, or hemorrhagic transformation of an ischemic infarct.
2. History of recent myocardial infarction (attributed to coronary artery disease) or unstable angina within the previous 3 months
3. Diabetic patients with history of myocardial infarction or coronary revascularization
4. History of familial hypercholesterolemia
5. Patients receiving proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors
6. Known diagnosis of severe dementia
7. Inability to obtain informed consent
8. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments.
9. Life expectancy of less than 24 months due to co-morbid terminal conditions.
10. Pre-morbid mRS >3
11. ICH score >3 upon presentation.
12. Contraindications to continuation/resumption of statin therapy, such as significant elevations of serum creatinine kinase and/or liver transaminases, and rhabdomyolysis
13. Woman of childbearing potential
14. Concurrent participation in another research protocol for investigation of experimental therapy.
15. Indication that withdrawal of care will be implemented for the qualifying ICH.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Statin; The same statin agent and dose that subjects were using at the time of ICH onset.	Drug: Statins; Statin drugs (already prescribed) at ICH onset will be either continued or discontinued by the participants following qualifying ICH; Other Names: HMG CoA
No Intervention: No-statin; Subjects will discontinue the statin agent that they were taking at the time of ICH onset. No placebo will be prescribed for these subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrent symptomatic ICH	within 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Major Adverse Cerebro- and Cardio-Vascular Events	Within 24 months

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Medical University of South Carolina; Johns Hopkins University; University Health Network, Toronto; Massachusetts General Hospital; Mayo Clinic; Baylor College of Medicine; University of Pennsylvania; University of California, San Diego; University of Maryland, Baltimore; Yale University; University of Alabama at Birmingham; Wayne State University; Columbia University; University of Pittsburgh; University of Michigan; University of Iowa; University of Wisconsin, Madison; Health Sciences Centre, Winnipeg, Manitoba; Montefiore Medical Center; Rush University Medical Center; University of Florida; University of Southern California; Brigham and Women's Hospital; Weill Medical College of Cornell University; Université de Sherbrooke; University of Alberta; Milton S. Hershey Medical Center; Wake Forest University Health Sciences; Oregon Health and Science University; University of California, San Francisco; Stanford University; State University of New York - Upstate Medical University; Ohio State University; The Ottawa Hospital; University of Minnesota; University of North Carolina, Chapel Hill; University of California, Irvine; George Washington University; Tufts Medical Center; Cedars-Sinai Medical Center; Temple University; Rhode Island Hospital; University of Utah; University of Virginia; Kaiser Permanente; The University of Texas Health Science Center at San Antonio; London Health Sciences Centre; University of Cincinnati; Thomas Jefferson University; Hopital de l'Enfant-Jesus; University of Arkansas; University of Kentucky; Spectrum Health Hospitals; Fraser Health; University of Nebraska; Aurora Health Care; Hartford Hospital; University of Louisville; University of South Alabama; University of New Mexico; Baystate Medical Center; University of Vermont Medical Center; North Shore University Hospital; Mount Sinai Hospital, New York; Carolinas Medical Center; Huntington Memorial Hospital; University of Kansas; West Virginia University; Ochsner Health System; Prisma Health-Upstate; Allina Health System; St. Joseph's Hospital and Medical Center, Phoenix; OSF Healthcare System; Swedish Medical Center; MetroHealth Medical Center; Staten Island University Hospital; Barnes-Jewish Hospital; Loyola University; Tampa General Hospital; Banner University Medical Center; Scripps Health; Foothills Medical Centre; New York Presbyterian Brooklyn Methodist Hospital; Froedtert Hospital; Lehigh Valley Hospital; San Francisco General Hospital; Jackson Health System; Abington Memorial Hospital; Aurora BayCare Medical Center; Long Beach Memorial Medical Center; St. Luke's Hospital, Kansas City, Missouri; Harborview Injury Prevention and Research Center; Central DuPage Hospital; Arrowhead Regional Medical Center; Lahey Hospital & Medical Center; Montreal Neurological Institute and Hospital; Regions Hospital; Canadian Stroke Consortium (CSC); McLaren Health Care; Intermountain Medical Center; UMASS Memorial Medical Center; Thunder Bay Regional Health Sciences Centre; St. Mary's Medical Center; NINDS Stroke Trials Network (StrokeNet); OU Medical Center; Metro Health, Michigan; Augusta University Medical Center; UH, Cleveland Medical Center; Buffalo General Medical Center; St. Joseph's Regional Medical Center, New Jersey; The Moses H. Cone Memorial Hospital; NYU Langone Medical Center - Tisch Hospital; NYU Langone Hospital - Brooklyn; Mercy San Juan Medical Center; Kaiser Permanente Fontana; Desert Care Network; Eden Medical Center; Sanford Medical Center Fargo; Baptist Medical Center Jacksonville; Mercy Health Saint Mary Grand Rapids; St. Cloud Hospital; York Hospital, York, PA; St. David's HealthCare; Tulane Medical Center; Legacy Emanuel Medical Center; Sacred Heart Medical Center Springfield; Cox Medical Center South; Hamilton General Hospital; Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre; Hopital de Chicoutimi

Publications and helpful links

General Publications

• Szejko N, Kirsch E, Falcone GJ. Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage. Curr Opin Lipidol. 2021 Aug 1;32(4):244-248. doi: 10.1097/MOL.0000000000000761.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 1, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: 2018C000515

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes